The present invention is a result of conducting the promising and pioneering research project led by the Korean Ministry of Education, Science and Technology, which had been hosted by Korea Institute of Science and Technology by 28 Feb. 2011 from 1 Apr. 2010, entitled “Development of a nitric oxide-releasing, blood-compatible stent” (Assignment No.: 20100002175).
Nitric (mon)oxide (NO) is a biomodulator exhibiting potency in a variety of fields. In 1992, NO was nominated as the “molecule of the year” by the American journal Science, and was the main research subject of the 1998 Nobel Prize in Physiology and Medicine. NO acts as a signaling molecule in the human body and is also formed as a product from an immune reaction. Physiological effects of NO encompass expansion of blood vessels, neurotransmission, regulation of the hair cycle, generation of reactive nitrogen-containing intermediates, regulation of penile erection, antibacterial effects, antivirus effects, and wound healing.
Among such physiological effects of NO, the expansion of blood vessels has received much attention. In vascular endothelial cells, NO transmits a signal for relaxation to the surrounding smooth muscle cells, whereby blood vessels expand and more blood flows therethrough. In addition, NO prevents contraction and growth of vascular smooth muscles and prevents aggregation of platelets in endothelia and adhesion of white blood cells to endothelia, contributing to maintaining homeostasis of blood vessels.
An angioplasty accompanying stent insertion is performed on patients with blocked coronary blood vessels due to accumulation of fat mass therein. In an angioplasty procedure, a small balloon is inserted into a blood vessel and then inflated, thereby forcing the fat mass tightly towards the walls of the blood vessel, and, as a result, the blood vessel is widened. In this regard, a tube-shaped mesh scaffold called a stent is inserted into the blood vessel, thereby forcibly maintaining the width of the blood vessel. In some cases, the blood vessel returns back to its narrow width, necessitating another angioplasty operation. Therefore, if one can find means to controllably release medications such as NO capable of preventing cell growth and inflammation from a stent, this may significantly contribute to a successful angioplasty procedure.
There are various compounds that are capable of releasing NO from the surface of an artificial implant such as a stent. Examples of the compounds include organic nitrates, esters, iron-nitrosyl complexs, sydnonimine, C-nitroso compounds, and S-nitrosothiols (R—S—NO). In particular, research into S-nitrosothiols has been actively conducted. Unfortunately, there has been cases where implants harboring these compounds failed to release NO into the human body and the rate of releasing NO is affected by the concentration of copper ions (Cu+). In addition, S-nitrosothiols are not stable themselves and thus difficult to obtain in a pure form.
Therefore, research into a novel material capable of more efficiently releasing NO and a method of more efficiently releasing NO has recently been actively conducted. Also, if the release of NO is more efficiently performed, an artificial implant needs to include a member capable for adjusting a rate of release occurring on a surface of the artificial implant.
A high concentration of NO is toxic, and since it is a vasodilator, an excess amount of NO in the human body can cause a total collapse of the circulatory system. Thus, a significant improvement in the performance of prosthetic implants can be achieved by developing a delivery system for releasing NO, which releases or, when necessary, suppresses or delays the release of an appropriate concentration of NO at an appropriate rate in response to signals from the surroundings, the release characteristics of which being unaffected by unwanted noise from the surroundings. When conventional NO delivery systems are used, an excess amount of NO is released at an early stage and it is thus difficult to achieve sustained release of NO.